Measurement of apparent exchange rates in biological tissue by double diffusion-weighted magnetic resonance imaging

扩散加权成像是一种广泛应用于医学成像的磁共振技术，尤其是在肿瘤和中风的诊断中。所测量的扩散系数允许人们间接推断关于组织结构的信息。例如，如果细胞膜受损，这可以通过增加的扩散系数来观察。然而，它往往是难以获得的直接关系之间的测量扩散系数和微观结构参数，如膜渗透性。在这方面的一种方法是最近提出的双扩散加权成像技术。这里，通过应用第二扩散加权序列块来扩展标准实验，该第二扩散加权序列块在由混合时间分开的第一扩散加权之后应用。如果存在具有不同扩散系数的几个隔室，则通过第一滤波器扩散加权对这些隔室进行不同的加权。具有较高扩散率的隔室被抑制。在混合时间期间，由于膜渗透性，不同隔室之间可能发生交换。因此，使用第二扩散加权测量的扩散系数取决于混合时间，并且对于大的混合时间接近平衡值。通过改变混合时间，可以测量出各室之间的表观交换率。在我们自己的准备工作中，对细胞培养物的初步测量是成功的。然而，首先，稳定的体内应用尚不可能。其次，测量参数和组织结构之间的关系仍然知之甚少。因此，该建议的一个目的是开发稳定的双扩散加权序列。为此，应开发更灵活的序列，利用该序列可以确定优化的定时和序列参数。应采用附加梯度，以尽量减少涡流伪影。对于细胞培养实验，应开发解耦体模固定装置，以使测量不易出现振动伪影。为了减少脉动伪影，计划在心脏周期上触发，以确保在心脏周期期间始终应用两个扩散权重。目前用于描述交换率对比度的模型非常简化，并且忽略了细胞膜对扩散过程的影响。为了对所获得的数据进行有用的解释，需要进行广泛的模拟和理论研究，其重点是膜几何形状和渗透性的影响。目的是研究真实交换率之间的关系，例如细胞内和细胞外空间之间的交换率，以及测量的表观交换率。最后，应通过对健康受试者和肿瘤患者的测量来评估交换率测量用于组织表征的潜力。

Diffusion-weighted imaging is a widely applied magnetic resonance technique in medical imaging, especially for tumor and stroke diagnosis. The measured diffusion coefficients allow one to deduce indirectly information about the tissue structure. If, for example, the cell membranes are damaged, this can be observed through an increased diffusion coefficient. However, it is often difficult to obtain a direct relation between the measured diffusion coefficient and microstructural parameters such as membrane permeability. An approach in this regard is the recently proposed double diffusion-weighted imaging technique. Here, the standard experiment is extended by applying a second diffusion weighting sequence block, which is applied after the first diffusion weighting separated by the mixing time. If several compartments with differing diffusion coefficients are present, these are weighted differently by the first filter diffusion weighting. The compartment with higher diffusivity is suppressed. During the mixing time, an exchange between the different compartments can occur due to membrane permeability. Consequently, the diffusion coefficient measured using the second diffusion weighting depends on the mixing time and approaches an equilibrium values for large mixing time. By varying the mixing time, an apparent exchange rate between the compartments can be measured.In our own preparatory work, initial measurements on cell cultures were successful. Firstly, however, a stable in vivo application is not yet possible. Secondly, the relation between the measured parameters and the tissue structure is still poorly understood. One aim of this proposal is thus to develop a stable double diffusion-weighted sequence. To this end, a more flexible sequence shall be developed, with which it becomes possible to determine optimized timing and sequence parameters. Additional gradients shall be implemented to minimize eddy current artifacts. For the cell culture experiments, decoupled phantom fixation devices shall be developed to make the measurements less prone to vibration artifacts. To reduce pulsation artifacts, triggering on the heart cycle is planned to be implemented to ensure that both diffusion weightings are always applied during the diastole.The currently used models for the description of the exchange rate contrast are very simplifying and neglect the influence of the cell membranes on the diffusion process. In order to come to a useful interpretation of the acquired data, extensive simulations and theoretical investigations are to be performed, whose focus will be on the influence of membrane geometry and permeability. The aim is to investigate the relationship between true exchange rates, e.g. between intra- and extracellular space, and the measured, apparent exchange rates.Finally, the potential of exchange rate measurements for tissue characterization shall be evaluated by measurements on healthy subjects and tumor patients.